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Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s disease
Open accessAbstract
BACKGROUND: Despite substantial research and development investment in Alzheimer's disease (AD), effective therapeutics remain elusive. Significant emerging evidence has linked cholesterol, β-amyloid and AD, and several studies have shown a reduced risk for AD and dementia in populations treated with statins. However, while some clinical trials evaluating statins in general AD populations have been conducted, these resulted in no significant therapeutic benefit. By focusing on subgroups of the AD population, it may be possible to detect endotypes responsive to statin therapy. METHODS: Here we investigate the possible protective and therapeutic effect of statins in AD through the analysis of datasets of integrated clinical trials, and prospective observational studies. RESULTS: Re-analysis of AD patient-level data from failed clinical trials suggested by trend that use of simvastatin may slow the progression of cognitive decline, and to a greater extent in ApoE4 homozygotes. Evaluation of continual long-term use of various statins, in participants from multiple studies at baseline, revealed better cognitive performance in statin users. These findings were supported in an additional, observational cohort where the incidence of AD was significantly lower in statin users, and ApoE4/ApoE4-genotyped AD patients treated with statins showed better cognitive function over the course of 10-year follow-up. CONCLUSIONS: These results indicate that the use of statins may benefit all AD patients with potentially greater therapeutic efficacy in those homozygous for ApoE4.
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“As lowering cholesterol in APOE4 carriers may decrease the risk of dementia based on other published literature [27, 28, 29, 30, 31, 32]”
From Blood PCSK9 Impacts Alzheimer's Disease Risk in an APOE Genotype‐Dependent Manner: A Prospective Cohort Study (2026) · cites this paper as [30]
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Metadata
- Authors
- Geifman, N., Brinton, R. D., Kennedy, R. E., Schneider, L. S., & Butte, A. J.
- Affiliations
- University of Manchester (GB)
- University of Alabama at Birmingham (US)
- University of Southern California (US)
- University of California, San Francisco (US)
- Corresponding author
- Geifman, Nophar
- Venue
- Alzheimer's Research & Therapy
- Published
- 2017-02-17
- Volume
- 9
- Issue
- 1
- Pages
- 10-10
- ISSN
- 1758-9193 (ISSN-L)
- PMC
- PMC5316146
- OpenAlex
- W2588146368
- Cited by
- 191
- References
- 77
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 20 · 2023: 19 · 2022: 30 · 2021: 22 · 2020: 24 · 2019: 18 · 2018: 28 · 2017: 8
- FWCI
- 2.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Alzheimer s Research & Therapy (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UA Campus Repository (The University of Arizona) (acceptedVersion, cc-by)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Research Explorer (The University of Manchester) (submittedVersion, other-oa)
- Funders
- National Institute on Aging (R34 AG049652)
- James H. Zumberge Faculty Research and Innovation Fund at the University of Southern California (NA)
- National Institutes of Health (R01 AG037561)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- statins, Alzheimer's disease, cognitive decline, simvastatin, APOE ε4, cholesterol, amyloid-beta, dementia risk, endotypes, statin therapy response, long-term statin use
- MeSH terms
- Alzheimer Disease, Humans, Nootropic Agents, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cognitive Dysfunction
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